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ALT flares during nucleotide analogue therapy are associated with HB sAg loss in genotype A HB eAg‐positive chronic hepatitis B
Author(s) -
Wong Darren,
Littlejohn Margaret,
Edwards Rosalind,
Jackson Kathy,
Revill Peter,
Gaggar Anuj,
Kitrinos Kathryn,
Subramanian Mani,
Marcellin Patrick,
ButiFerret Maria,
Janssen Harry,
Gane Ed,
Locarnini Stephen,
Thompson Alexander
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13716
Subject(s) - medicine , gastroenterology , flare , alanine aminotransferase , genotype , chemistry , biochemistry , physics , astrophysics , gene
Background Alanine aminotransferase ( ALT ) flares during NA therapy are uncommon but occur. Evaluation of ALT flares during nucleos(t)ide analogue ( NA ) therapy is important as new immunomodulatory therapies for hepatitis B virus ( HBV ) are developed. We evaluated the association between ALT flares and HB sAg loss during long‐term therapy for genotype A CHB . Methods This analysis included genotype A subjects from a phase III study of tenofovir vs adefovir in HB eAg‐positive HBV . ALT flare was defined as (i) a rise in ALT >2x ULN from normal ALT levels; or (ii) a rise in ALT >2x baseline ALT level. HB sAg response at week 384 was recorded as one of HB sAg loss vs HB sAg decline (≥1 log 10 IU /mL decline) vs non‐response. The primary analysis evaluated the association between ALT flare and HB sAg response. Results 54 subjects were included. 23/54 (43%) subjects experienced an on‐treatment ALT flare. 45% achieved an HB sAg reduction ≥1 log 10 IU / mL , and of these 67% achieved HB sAg loss at a median of 102 weeks [ IQR : 64‐156]. Flare was associated with HB sAg decline vs non‐response (67% vs 23%, P = .002), and were more common in subjects who achieved HB sAg loss vs non‐response (56% vs 23%), P = .049). There was a median delay of 56 weeks [ IQR : 40‐80] between a flare and HB sAg loss. Conclusion In genotype A subjects undergoing long‐term NA therapy, ALT flares predict for HB sAg response. The delay between ALT flare and HB sAg loss has implications for clinical trial design for early phase development of immunomodulatory strategies aiming for HB sAg loss.